Different Types of Connections between the Thalamus and Vestibular Nucleus in the Human Brain

doi:10.21203/rs.3.rs-4700390/v1

Download PDF

Article

Different Types of Connections between the Thalamus and Vestibular Nucleus in the Human Brain

https://doi.org/10.21203/rs.3.rs-4700390/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

This study investigated connections between vestibular and thalamic nuclei in the human brain using diffusion tensor imaging (DTI). We examined nine vestibulothalamic tracts (VTTs) by selecting three seed regions of interest (ROIs) in the vestibular nuclei (superior, medial, and lateral) and three target ROIs in the thalamic nuclei (ventral posterolateral, ventral posteromedial, and ventral intermediate). DTI tractography was performed on twelve healthy subjects. Results showed all three vestibular nuclei had connectivity with the thalamus, with varying reconstruction rates. The lateral vestibular nucleus demonstrated highest connectivity with ventral posterolateral and posteromedial nuclei, while the medial vestibular nucleus had highest connectivity with the ventral intermediate nucleus. All VTTs passed through the midbrain tegmentum, with some traversing the tectum. This study provides new insights into neural pathways involved in vestibular information processing and may serve as a foundation for understanding the central vestibular system's neurophysiology. These findings could have implications for diagnosing and treating vestibular disorders and related balance issues.

The vestibular nuclei comprise a group of nuclei in the brainstem that play a crucial role in balance, spatial perception, and eye movement control. This complex receives input from the vestibular system in the inner ear, which detects changes in head position and movement. There are four types of vestibular nuclei (superior, inferior, medial, and lateral), all involved in controlling head, neck, and eye movements. The vestibular nuclei in the brainstem are primarily connected to the cerebellum and various thalamic nuclei through the c (VTT).

The thalamus plays a vital role in relaying sensory and motor signals to the cerebral cortex. It is also involved in motor control, receiving input from the cerebellum, vestibular nuclei, and basal ganglia, sending motor signals to the motor cortex, and aiding in the coordination of voluntary movements. Thalamocortical connections are bidirectional, crucial for integrating and coordinating sensory inputs.

Thalamic nuclei related to the vestibular system include the ventral posterolateral (VPL), ventral posteromedial (VPM), and ventral intermediate (VI) nuclei. While multiple projections between the vestibular and thalamic nuclei have been reported, the exact patterns of these connections in the human brain are not yet fully understood.

The aim of this study is to use diffusion tensor imaging (DTI) analysis to examine the various connections between the vestibular and thalamic nuclei in the human brain, and to further reveal their relay pathways. This research will provide new insights into the neural pathways involved in vestibular information processing and serve as a foundation for understanding the neurophysiology of the central vestibular system.

We collected DTI data from 12 healthy adults and analyzed nine vestibulothalamic tracts between the vestibular nuclei (superior, medial, and lateral) and thalamic nuclei (VPL, VPM, and VI). The results of this study have potential applications in the diagnosis and treatment of vestibular disorders and related balance issues.

The vestibular nuclei comprises a group of nuclei located in the brainstem that play a crucial role in processing information related to balance, spatial orientation, and coordination of eye movements.[1, 2] This complex receives input from the vestibular system, a sensory system in the inner ear responsible for detecting changes in head position and movement.[2] There are four types of vestibular nuclei (the superior, inferior, medial, and lateral), all of which play a role in controlling head, neck, and eye movements.[3] The vestibular nuclei in the brainstem are primarily connected to the cerebellum and various thalamic nuclei through the vestibulothalamic tract (VTT).[4] The primary function of the VTT is to transmit information from the vestibular nuclei to the thalamus. This information is crucial for integrating the vestibular signals with other sensory information, including visual and proprioceptive inputs.[4, 5]

The thalamus plays a crucial role in relaying sensory and motor signals to the cerebral cortex, further contributing to various functions in the central nervous system. It acts as a relay station for sensory information from various sensory organs to corresponding areas of the cerebral cortex.[6] In addition to relaying sensory information, the thalamus is also involved in motor control, receiving input from the cerebellum, vestibular nucleus, and basal ganglia, sending motor signals to the motor cortex, and aiding in the coordination of voluntary movements.[7] Thalamocortical connections are bidirectional, meaning that information flows from the thalamus to the cortex, and vice versa. These connections are vital for integrating and coordinating sensory inputs, thus allowing the brain to form coherent perceptions of the surrounding environment.[6, 8, 9]

The term "thalamic nucleus" refers to a group of cell bodies (neurons) located within the thalamus, which is a core structure of the brain. It comprises several individual nuclei, each with a specific function, which are broadly categorized into relay nuclei, which transmit sensory information to the cortex, and association nuclei, which are involved in information integration and processing.[6, 10] In addition to sensory processing, the thalamus plays a role in relaying functions such as movement, consciousness, memory, and emotion.[7, 11] Nuclei related to the vestibular system include the ventral posterolateral (VPL), ventral posteromedial (VPM), and ventral intermediate (VI). Multiple projections between the vestibular and thalamic nuclei have also been reported.[4, 12, 13]

In this context, the present study aimed to use diffusion tensor imaging (DTI) analysis to examine the various connections between the vestibular and thalamic nuclei in the human brain, and to further reveal their relay pathways.

In the current study, we implemented nine tracts by selecting three seed ROIs (the SuVN, MVN, and LVN) and three target ROIs (the VPL, VPM, and VI). Each of the nine VTT pathways originates from the pontine VN and terminates on the caudal side of the thalamic nucleus. The reconstruction rate of the VTT to the VPL was the highest in the LVN (95.8%), followed by the SuVN (62.5%) and MVN (41.7%). The reconstruction rate of the VTT to the VPM was also highest in the LVN (83.3%), followed by the SuVN (75.0%) and MVN (58.3%). The reconstruction rate of the VTT to the VI was the highest in the MVN (75.0%), followed by the SuVN (70.8%) and MVN (66.7%)(Table 1).

The analyzed VTT was connected to the thalamic nucleus through the tegmentum and tectum of the midbrain, and the rate of passage through the tegmentum was higher than through the tectum. The VTT originating from the SuVN, MVN, and LVN passes through the tegmentum area of the midbrain, and is connected to the VPL, VPM, and VI areas. In contrast, for VTTs from the SuVN, the proportion connected to the thalamus via the tectum was 33.3% for the VPL, 38.9% for the VPM, and 41.2% for the VI. For the VTTs from the MVN, the proportion connected to the thalamus via the tectum was 20.0% for the VPL, 7.1% for the VPM, and 22.2% for the VI. However, among VTTs originating from the LVN, there were no connections to the thalamus via the tectum (Table 2).

The purpose of this study was to analyze the VTT between the three vestibular nuclei and three thalamic nuclei using DTI, and to compare the characteristics of each connectivity. The results of this study showed that all three vestibular nuclei had a certain level of connectivity with the thalamus. The vestibular nuclei are located in the brainstem, specifically within the pons and medulla oblongata, and there are four main nuclei: the superior, inferior, medial, and lateral VN.[3] This study examined the connections between the VPL, VPM, and VI thalamic nuclei and three vestibular nuclei: the lateral, medial, and superior nuclei. The LVN primarily aids the vestibulospinal reflexes to maintain posture and balance, with mediation by the paravertebral and proximal extensor muscles.[16, 17] The MVN facilitates the vestibulo-ocular reflex and ensures clear vision during horizontal head movement.[18] Meanwhile, the SVN is associated with the perception of gravity and body movement.[3] Given this knowledge, the present study aimed to understand how these thalamic nuclei connect with the vestibular nuclei, in order to shed light on the neural pathways involved in sensory processing and motor coordination related to balance, posture, and vision.

The VPL area is known to be a major connection area n vestibulothalamic projections; however, it is not specialized only for vestibular function, showing connectivity with other peripheral sensory and cortical areas.[19] Overall, the results of this study showed that the was LVN was then vestibular nucleus with the highest connectivity with the VPL, while the SuVN and MVN showed relatively low connectivity (Table 2). The neurological connectivity between the vestibular nuclei and VPM area remains poorly understood. However, several studies have shown that VPM neurons respond directly to vestibular nerve stimulation, as well as to rotational and translational movements associated with vestibular sensation.[4, 20] In this study, the VPM thalamic nucleus also showed the highest connectivity with the LVN, followed by the SuVN and MVN. The VI plays a central role in motor control in the thalamic nucleus, and is particularly involved in the coordination of muscle activity and limb movement during voluntary movements of the human body.[20, 21] The VI is also considered a target area for deep brain stimulation to alleviate tremor symptoms in patients with Parkinson’s disease.[22] Conversely, relatively little is known about the neurological connectivity with the vestibular region. In the present study, the MVN showed the highest connectivity with the VI, followed by the SuVN and LVN.

Table 1

Comparison of reconstruction rates between the vestibular and thalamic nuclei
ROIs	VPL		VPM		VI
ROIs	Recon	Non-recon	Recon	Non-recon	Recon	Non-recon
SuVN	15 (62.5%)	9 (37.5%)	18 (75.0%)	6 (25.0%)	17 (70.8%)	7 (29.2%)
MVN	10 (41.7%)	14 (58.3%)	14 (58.3%)	10 (41.7%)	18 (75.0%)	6 (25.0%)
LVN	23 (95.8%)	1 (4.2%)	20 (83.3%)	4 (16.7%)	16 (66.7%)	8 (33.3%)

ROIs: region of interest; SuVN: superior vestibular nuclei; MVN: medial vestibular nuclei; LVN: lateral vestibular nuclei; VPL: ventral posterolateral; VPM: ventral posteromedial; VI: ventral intermediate; Recon: reconstructed; Non-recon: Non-reconstructed.

Table 2

Tectum and tegmentum passage rates of the 9 VTT
ROIs	VPL		VPM		VI
ROIs	Tegmentum	Tectum	Tegmentum	Tectum	Tegmentum	Tectum
SuVN	15/15 (100.0%)	5/15 (33.3%)	18/18 (100.0%)	7/18 (38.9%)	17/17 (100.0%)	7/17 (41.2%)
MVN	10/10 (100.0%)	2/10 (20.0%)	14/14 (100.0%)	1/14 (7.1%)	18/18 (100.0%)	4/18 (22.2%)
LVN	23/23 (100.0%)	0/23 (0.0%)	20/20 (100.0%)	0/20 (0.0%)	16/16 (100.0%)	0/16 (0.0%)
ROIs: regions of interest, SuVN: superior vestibular nuclei, MVN: medial vestibular nuclei, LVN: lateral vestibular nuclei, VPL: ventral posterolateral, VPM: ventral posteromedial, VTT: vestibulothalamic tract; VI: ventral intermediate

In this study, we found that all connection paths between the three vestibular nuclei and the thalamic nucleus passed through the tegmental area of the midbrain, whereas connectivity with the tectum was relatively low or absent in some cases (Fig. 2). The tegmentum is the ventral part of the midbrain, and is primarily involved in visual and auditory information processing, motor control, and autonomic nervous system function.[23] In 2008, Zwergal et al.[24] investigated the correlation between ocular tilt reaction problems and interstitial nuclei of Cajal in patients with brainstem lesions. Our results confirmed that 96% of the patients with ocular tilt reactions had damage to the paramedian posterior tegmentum related to the medial longitudinal fascicle. The tectum refers to the dorsal midbrain, which plays an important role in processing visual and auditory information. However, little research has been conducted on the anatomical and functional relationships between the tectum and vestibular system. Nevertheless, several studies have shown that the tectum, along with the visual cortex, is important for gaze stabilization related to vestibular function.[25, 26] Therefore, the tegmentum area of the midbrain is thought to function as the main relay pathway in the connectivity between the vestibular nuclei and the thalamic nuclei, while the tectum is believed to be able to contribute to some extent.

Several previous studies using animal models or neuroimaging analysis methods in the human brain have reported on the neurological connectivity between the vestibular and thalamic nuclei. In 1999, Shiroyama et al.[27] reported on the connectivity between each vestibular and thalamic nucleus in rats using the anterograde axonal tracer method. Injections into the SuVN and lateral VN showed connectivity with various thalamic nuclei, including the VPL, VPM, and VL. Injections into the MVN showed major connectivity with the VPM, and minor connectivity with the VPL and posterior thalamic nucleus. In 2002, Bácskai et al.[28] reported on the ascending and descending projection pathways of the lateral VN in rats. The ascending projection of the lateral VN passes through the medial longitudinal fasciculus to the thalamus, and predominantly terminates at the caudal one-third of the thalamus. The VPM is the area with the highest density. Additionally, previous studies have suggested the existence of an ipsilateral VTT in the human brain.[29–32] Based on the results of previous studies, it can be assumed that the ipsilateral VTT originates around the medial lemniscus and is connected to the posterolateral thalamus.[29] In 2018, Jang and Kwon[30] investigated and reported the anatomical characteristics of the ipsilateral VTT in the human brain using DTI. The reconstructed ipsilateral VTT was connected posterolaterally to the upper pons and anteromedially to the upper midbrain, situated between the vestibular and lateral thalamic nuclei.

In conclusion, this study analyzed and compared the VTT from three vestibular nuclei (the SVN, MVN, and LVN) to the VPL, VPM, and VI thalamic nuclei in young adults. The results showed that the VTT from the three vestibular nuclei to the thalamus were different, but all were connected through the tegmentum and tectum regions of the midbrain. Therefore, this study provides basic data on the processes by which peripheral vestibular information is transmitted to the central nervous system, and can serve as neurophysiological data for the central vestibular system. However, this study has several limitations that should be considered. First, it targeted only a small number of adults; therefore, the results cannot be generalized. Secondly, it was difficult to locate an accurate ROI because of the diminutive size of the VN and thalamic nucleus. Finally, only the connectivity between the ipsilateral VN and the thalamic nucleus was analyzed, while the contralateral connection was not analyzed. Therefore, in future studies, it will be necessary to study the bilateral connectivity between the VN and thalamic nucleus by recruiting a larger number of subjects of various ages.

Data availability

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (R-2024-00380).

Author contributions

Conceptualization: S.S.Y., S.S.L; Methodology: S.S.Y.; Sofware: S.S.Y.; Investigation: S.S.Y.;Resources: S.S.Y.; Data curation: S.S.L.; Writing and original draf preparation: S.S.L.; Writing, review, and editing: S.S.Y.; Visualization: S.S.L.; Supervision: S.S.Y.; Project administration: S.S.L., S.S.Y.; Funding acquisition: S.S.Y., All authors have read and agreed to the fnal version of the manuscript.

Competing interests

The authors declare no competing interests.

Hernandez, E. Neuroanatomy, nucleus vestibular. (2020).
Khan, S. & Chang, R. Anatomy of the vestibular system: a review. NeuroRehabilitation 32, 437-443 (2013).
Highstein, S. M. & Holstein, G. R. The anatomy of the vestibular nuclei. Progress in brain research 151, 157-203 (2006).
Wijesinghe, R., Protti, D. A. & Camp, A. J. Vestibular interactions in the thalamus. Frontiers in Neural Circuits 9, 79 (2015).
Maciewicz, R., Phipps, B., Bry, J. & Highstein, S. The vestibulothalamic pathway: contribution of the ascending tract of Deiters. Brain research 252, 1-11 (1982).
Lee, T.-N. Thalamic neuron theory: theoretical basis for the role played by the central nervous system (CNS) in the causes and cures of all diseases. Medical Hypotheses 43, 285-302 (1994).
Sommer, M. A. The role of the thalamus in motor control. Current opinion in neurobiology 13, 663-670 (2003).
Jones, E. G. A new view of specific and nonspecific thalamocortical connections. Advances in neurology 77, 49-71; discussion 72 (1998).
Nakajima, M. & Halassa, M. M. Thalamic control of functional cortical connectivity. Current opinion in neurobiology 44, 127-131 (2017).
Pinault, D. The thalamic reticular nucleus: structure, function and concept. Brain research reviews 46, 1-31 (2004).
Ward, L. M. The thalamus: gateway to the mind. Wiley Interdisciplinary Reviews: Cognitive Science 4, 609-622 (2013).
Wild, J. M. Vestibular projections to the thalamus of the pigeon: an anatomical study. Journal of Comparative Neurology 271, 451-460 (1988).
De Waele, C., Baudonnière, P., Lepecq, J., Tran Ba Huy, P. & Vidal, P. Vestibular projections in the human cortex. Experimental brain research 141, 541-551 (2001).
Galons, J. P. Diffusion weighted and diffusion tensor imaging: A clinical guide. Journal of Magnetic Resonance Imaging 46, 1230-1231 (2017).
Warren, S., Capra, N., Yezierski, R., Haines, D. & Mihailoff, G. The somatosensory system I: tactile discrimination and position sense. Fundamental Neuroscience for Basic and Clinical Applications, 243-257 (2018).
Barnes, C. & Pompeiano, O. The contribution of the medial and lateral vestibular nuclei to presynaptic and postsynaptic effects produced in the lumbar cord by vestibular volleys. Pflügers Archiv 317, 1-9 (1970).
Lacour, M. & Borel, L. Vestibular control of posture and gait. Archives Italiennes de Biologie 131, 81-104 (1993).
Fetter, M. Vestibulo-ocular reflex. Neuro-Ophthalmology 40, 35-51 (2007).
Lopez, C. & Blanke, O. The thalamocortical vestibular system in animals and humans. Brain research reviews 67, 119-146 (2011).
Marlinski, V. & McCrea, R. A. Activity of ventroposterior thalamus neurons during rotation and translation in the horizontal plane in the alert squirrel monkey. Journal of neurophysiology 99, 2533-2545 (2008).
Bertino, S. et al. Ventral intermediate nucleus structural connectivity-derived segmentation: anatomical reliability and variability. Neuroimage 243, 118519 (2021).
Wakim, A. A. et al. Direct targeting of the ventral intermediate nucleus of the thalamus in deep brain stimulation for essential tremor: a prospective study with comparison to a historical cohort. Journal of Neurosurgery 136, 662-671 (2021).
Bassett, J. P. & Taube, J. S. Neural correlates for angular head velocity in the rat dorsal tegmental nucleus. Journal of Neuroscience 21, 5740-5751 (2001).
Zwergal, A. Unilateral INO is associated with ocular tilt reaction in pontomesencephalic lesions.
Wibble, T., Pansell, T., Grillner, S. & Pérez-Fernández, J. Conserved subcortical processing in visuo-vestibular gaze control. Nature communications 13, 4699 (2022).
Kardamakis, A. A., Perez-Fernandez, J. & Grillner, S. Spatiotemporal interplay between multisensory excitation and recruited inhibition in the lamprey optic tectum. Elife 5, e16472 (2016).
Shiroyama, T., Kayahara, T., Yasui, Y., Nomura, J. & Nakano, K. Projections of the vestibular nuclei to the thalamus in the rat: a Phaseolus vulgaris leucoagglutinin study. Journal of Comparative Neurology 407, 318-332 (1999).
Bácskai, T., Szekely, G. & Matesz, C. Ascending and descending projections of the lateral vestibular nucleus in the rat. Acta Biologica Hungarica 53, 7-21 (2002).
Zwergal, A., Büttner-Ennever, J., Brandt, T. & Strupp, M. An ipsilateral vestibulothalamic tract adjacent to the medial lemniscus in humans. Brain 131, 2928-2935 (2008).
Jang, S. H. & Kwon, H. G. The ipsilateral vestibulothalamic tract in the human brain. Translational Neuroscience 9, 22-25 (2018).
Jang, S. H. & Kwon, H. G. Injury of the ipsilateral vestibulothalamic tract in a patient with pontine hemorrhage. Acta Neurologica Belgica 120, 951-954 (2020).
Lang, W., Büttner-Ennever, J. & Büttner, U. Vestibular projections to the monkey thalamus: an autoradiographic study. Brain research 177, 3-17 (1979).

No competing interests reported.

Download PDF

Reviewers agreed at journal
25 Jul, 2024
Reviewers invited by journal
19 Jul, 2024
Editor assigned by journal
19 Jul, 2024
Editor invited by journal
15 Jul, 2024
Submission checks completed at journal
15 Jul, 2024
First submitted to journal
07 Jul, 2024

You are reading this latest preprint version

Different Types of Connections between the Thalamus and Vestibular Nucleus in the Human Brain

Status:

Version 1

Abstract

Figures

Background & Summary

Introduction

Methods

Results

Discussion

Declarations

References

Additional Declarations

Status:

Version 1